Appendix 1: Full literature search terms
1. *Abdominal Pain/co, di, et [Complications, Diagnosis, Etiology]
2. *Fatigue/co, di, et [Complications, Diagnosis, Etiology]
3. *Gastrointestinal Hemorrhage/co, di, et [Complications,Diagnosis, Etiology]
4. *Anemia, Hypochromic/co, di, et [Complications, Diagnosis, Etiology]
5. *Intestinal Obstruction/co, di, et [Complications, Diagnosis, Etiology]
6. *Constipation/co, di, et [Complications, Diagnosis, Etiology]
7. *Diarrhea/co, di, et [Complications, Diagnosis, Etiology]
8. *Anorexia/co, di, et [Complications, Diagnosis, Etiology]
9. *nausea/co, di, et [Complications, Diagnosis, Etiology]
10. *Dyspepsia/co, di, et [Complications, Diagnosis, Etiology]
11. *Flatulence/co, di, et [Complications, Diagnosis, Etiology]
12. Symptom$.mp.
13. *Weight Loss/
14. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13
15. exp Abdominal Pain/co, di, et [Complications, Diagnosis, Etiology]
16. exp Fatigue/co, di, et [Complications, Diagnosis, Etiology]
17. exp Gastrointestinal Hemorrhage/co, di, et [Complications,Diagnosis, Etiology]
18. exp Anemia, Hypochromic/co, di, et [Complications, Diagnosis, Etiology]
19. exp Intestinal Obstruction/co, di, et [Complications, Diagnosis, Etiology]
20. exp Constipation/co, di, et [Complications, Diagnosis, Etiology]
21. exp Diarrhea/co, di, et [Complications, Diagnosis, Etiology]
22. exp Anorexia/co, di, et [Complications, Diagnosis, Etiology]
23. exp nausea/co, di, et [Complications, Diagnosis, Etiology]
24. exp Dyspepsia/co, di, et [Complications, Diagnosis, Etiology]
25. exp Flatulence/co, di, et [Complications, Diagnosis, Etiology]
26. Symptom$.mp.
27. exp Weight Loss/
28. 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27
29. Abdominal Pain/co, di, et [Complications, Diagnosis, Etiology]
30. FATIGUE/co, di, et [Complications, Diagnosis, Etiology]
31. Gastrointestinal Hemorrhage/co, di, et [Complications,Diagnosis, Etiology]
32. Anemia, Hypochromic/co, di, et [Complications, Diagnosis, Etiology]
33. Intestinal Obstruction/co, di, et [Complications, Diagnosis, Etiology]
34. Constipation/co, di, et [Complications, Diagnosis, Etiology]
page 1 of 13
35. Diarrhea/co, di, et [Complications, Diagnosis, Etiology]
36. Anorexia/co, di, et [Complications, Diagnosis, Etiology]
37. Nausea/co, di, et [Complications, Diagnosis, Etiology]
38. Dyspepsia/co, di, et [Complications, Diagnosis, Etiology]
39. Flatulence/co, di, et [Complications, Diagnosis, Etiology]
40. Symptom$.mp.
41. Weight Loss/
42. 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41
43. exp *Abdominal Pain/co, di, et [Complications, Diagnosis, Etiology]
44. exp *Fatigue/co, di, et [Complications, Diagnosis, Etiology]
45. exp *Gastrointestinal Hemorrhage/co, di, et [Complications,Diagnosis, Etiology]
46. exp *Anemia, Hypochromic/co, di, et [Complications, Diagnosis, Etiology]
47. exp *Intestinal Obstruction/co, di, et [Complications, Diagnosis, Etiology]
48. exp *Constipation/co, di, et [Complications, Diagnosis, Etiology]
49. exp *Diarrhea/co, di, et [Complications, Diagnosis, Etiology]
50. exp *Anorexia/co, di, et [Complications, Diagnosis, Etiology]
51. exp *nausea/co, di, et [Complications, Diagnosis, Etiology]
52. exp *Dyspepsia/co, di, et [Complications, Diagnosis, Etiology]
53. exp *Flatulence/co, di, et [Complications, Diagnosis, Etiology]
54. Symptom$.mp.
55. exp *Weight Loss/
56. 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55
57. exp Colorectal Neoplasms/pp, co, di, et [Physiopathology, Complications, Diagnosis,
Etiology]
58. exp Rectal Diseases/pp, co, di, et [Physiopathology,Complications,Diagnosis, Etiology]
59. exp Colonic Diseases/pp, co, di, et [Physiopathology,Complications,Diagnosis, Etiology]
60. 57 or 58 or 59
61. exp *Colorectal Neoplasms/pp, co, di, et [Physiopathology, Complications, Diagnosis,
Etiology]
62. exp *Rectal Diseases/pp, co, di, et [Physiopathology,Complications,Diagnosis, Etiology]
63. exp *Colonic Diseases/pp, co, di, et [Physiopathology,Complications,Diagnosis, Etiology]
64. 61 or 62 or 63
65. 14 and 60
66. 14 and 64
67. 28 and 60
68. 28 and 64
page 2 of 13
69. 42 and 60
70. 42 and 64
71. 56 and 60
72. 56 and 64
73. 65 and 66
74. 67 and 68
75. 69 and 70
76.71 and 72
77.73 or 74 or 75 or 76
page 3 of 13
Appendix 2: Data extraction: data extracted, with definitions and categories used for analysis
Study Descriptors
Data Extraction: Assumptions made/definitions used
Details of papers
Year of
The years in which the papers in the systematic review were
publication
published extended from 1960 to 2005. We categorised the year of
publication into 3 categories: before 1990; 1991-2000, and after
2000.
Publication year
Papers (n)
Up to 1990
13
1991-2000
22
From 2001
27
Papers (n)
Prospective or
We defined studies as prospective if patients were recruited after
retrospective
the study criteria were defined.
Prospective
We defined studies as retrospective if the data was collected from
Unknown
data already available and collected for other purposes. This
control studies)
39
(includes
case
23
included sources such as medical records or databases.
Information
We assessed how the symptom information used in the study was
source
elicited. We grouped these into whether or not the information was
collected purposely for the study. Information collected purposely
Summary
Papers
(n)
Purposely collected
46
completed by the patient), or from a history and clinical examination
Not purposely collected
13
done as part of the study. Information not collected purposely was
Not stated
3
for the study was by questionnaire (administered by a clinician or
taken from the patients’ medical record.
Table continued on next page
page 4 of 13
Appendix 2: Data extraction: data extracted, with definitions and categories used for analysis (continued)
Study Descriptors
Data Extraction: Assumptions made/definitions used
Patient recruitment:
In some studies it was not stated if the recruitment was
consecutive or not?
consecutive or not. Where this occurred, if it was obvious
form the design, the appropriate recruitment was recorded.
However, in some papers this was not possible to identify, and
’not stated’ was recorded. Assumption made: if data was
Details of papers
Summary
Papers (n)
Yes
39
Unknown(includes case
control studies
23
taken retrospectively from a database of endoscopy patients,
it was assumed that consecutive patients were recruited.
Study type
Some studies were cross sectional in design, but had an
Study Design
additional component of follow up. These studies were
Cross sectional analytical
42
classified as cross-sectional.
Case control
14
Cohort
5
Combined: cohort and case
review
1
If there was doubt about a study type, the higher quality study
type was chosen – this optimises results.
Patient source: clinical
The majority of patients were recruited or identified from
setting of the study
endoscopy units or radiology centres. Data was extracted
Summary
Papers (n)
Papers (n)
19
Patients were also recruited from other clinical settings. The
General practice (including
screening, community)
Specialist
clinical setting was summarised into those from general
Mixed (case control)
14
about the source of referral of these patients to these units.
practice and those from a specialist setting.
page 5 of 13
29
Appendix 2: Data extraction: data extracted, with definitions and categories used for analysis (continued)
Study Descriptors
Data Extraction: Assumptions made/definitions used
Population type:
In some studies patients in the study all had symptoms, while in
others asymptomatic patients were also included. In addition,
some papers presented information from a population of all
bleeders: in these papers information was also provided about
symptoms other than bleeding.
Symptoms present
in study population
Details of papers
We grouped the papers into those where all the participants
had symptoms and those in which asymptomatic people were
also included.
Number of
symptoms reported
per patient
Studies differed in how they reported the presence of
symptoms. In some studies, patients could have more than one
symptom/indication for colonoscopy recorded,(ie non-mutually
exclusive) while in others only 1 symptom or indication was
recorded (ie symptoms were mutually exclusive). The
significance of this is that in non-mutually exclusive papers it is
likely that all symptoms present were recorded, whereas in
mutually exclusive papers it was possible (and indeed likely) that
patients had additional symptoms that were not reported. In
only 1 paper was the hierarchy for the reporting of symptoms
recorded.
Symptom background
Papers (n)
Included symptomatic and
asymptomatic people
All FOBT +ve
All people had bleeding
All symptomatic (asymptomatic
people symptoms not included)
40
Number of symptoms reported
Papers (n)
1
7
15
Maximum of 1 per patient
19
Any number reported
43
Table continued on next page
page 6 of 13
Appendix 2: Data extraction: data extracted, with definitions and categories used for analysis (continued)
Study Descriptors
Data Extraction: Assumptions made/definitions used
Ease with which
The quality of the data analysis and presentation varied in the
papers; in some cases major assumptions about either the
study or the figures given needed to be made. Data extraction
was categorised as listed below, with the assumptions made to
rectify problems identified:
data relevant to the
systematic review
was available in
paper
Details of papers

Easy (all information in the paper);

all information is in the paper, but with minor
miscalculations (usually typographical errors) of numbers
with rectification obvious; obvious corrections made

all information in the paper, but with minor miscalculations
where rectification was not obvious; calculation made using
other data provided – for eg discrepancy between data
provided in a table and in the text: assumption made: use
data in table, unless obviously incorrect; use table providing
the most information, or most consistent information.

all information was in the paper, but data required needed
to be recalculated (however, the results do not equal other
values in paper – eg OR);

major assumptions were needed to extract figures: for
example if the denominator is known, use maximum
number of people participating in a study)

assumptions were needed about the methodology
Data accessibility
Papers (n)
Easy/minor issues
52
Major issues
10
Note: There were 2 papers with 2 problems and 1
paper with 3 problems.
Table continued on next page
page 7 of 13
Appendix 2: Data extraction: data extracted, with definitions and categories used for analysis (continued)
VALIDITY CRITERIA
Reference standard
Studies used a range of reference standards: colonoscopy,
sigmoidoscopy (flexible or rigid), barium enema, clinical follow
up or a combination of these. One study did not have a single
reference standard, but used multiple diagnostic modalities.
4 studies were case control studies: cases were diagnosed by
colonoscopy, but the controls had no verification
page 8 of 13
Diagnostic test used
Papers (n)
Colonoscopy
28
All others
34
Appendix 3: Characteristics of studies of symptoms and colorectal cancer or polyps
Pop
Mut
Design
No in
Cancer
Polyp
Type
Excl
Type
study
(n)
(n)
2007
S+N
1
xs
16-87
1,398
11
214
X
Ahmed
2005
B
2
xs
50-69
563
43
279
X
Bafandeh
2008
S
2
xs
480
16
56
X
Bat
1992
S+N
2
xs
80 -101
436
29
130
X
Berkowitz
1993
S+N
1
xs
15-93
448
16
59
Bhatti
2004
S
2
xs
40-70
50
Bjerregaard
2007
S
2
xs
40-97
Brenna
1990
S+N
1
Brewster
1994
S
Chak
1996
Charalambopoulos
Author
Year
Adler
age range
Bleeding
Abdo
pain
CBH
X
X
X
X
X
X
17
X
X
2,172
122
X
X
xs
833
45
203
X
2
xs
462
21
60
X
S+N
2
xs
21-99
653
28
2000
S
1
xs
23-82
795
3
207
X
X
X
Cheong
2000
S+N
1
xs
13-92
375
22
53
X
X
X
Curless
1994
S+N
2
cc
20-99
546
273
X
X
X
1,144
51
X
X
Constip
Diarrhoea
X
X
X
X
X
X
X
Weight
loss
Other
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
(17 pts<40)
de Bossett
2002
S+N
1
xs
16-95
Douek
1999
S
1
xs
455
64
Dukas
2000
S+N
2
c
84,438
611
104
page 9 of 13
X
X
X
X
Pop
Mut
Design
No in
Cancer
Polyp
Type
Excl
Type
study
(n)
(n)
2006
S+N
1
xs
80+
1,199
45
108
X
du Toit
2006
S+N
2
xs
45-75
2,889
38
33
X
Ellis
2005
B
2
xs
35-89+
266
11
17
Farrands
1985
S
2
xs
30-80+
(majority
50-70)
152
13
Ferraris
2004
S+N
1
xs
55-64
8,507
46
Fitjen
1995
B
2
xs
18 -75
269
9
Fontagnier
2000
S+N
1
xs
80-94
157
27
Haenszel
1973
S+N
2
cc
536
179
Hamilton
2005
S+N
2
cc
2,093
349
Higginson
1966
S+N
2
cc
1,360
340
X
Jacobs
1998
S+N
2
cc
838
424
X
Jain
1980
S+N
2
cc
1619
542
X
Jensen
1993
S
2
xs
52 – 74
149
5
10
X
X
X
X
Kassa
1996
S+N
1
sx
11 – 83
640
45
59
X
X
X
X
Kojima
2004
S+N
2
c
62,929
649
X
Kune
1988
S+N
2
cc
1408
685
X
Lee
2002
S
2
xs
869
43
Author
Year
Duncan
age range
30-62
14-91
Bleeding
pain
CBH
Constip
Diarrhoea
Weight
loss
X
Other
X
X
X
1,398
Abdo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
page 10 of 13
X
X
X
Pop
Mut
Design
No in
Cancer
Polyp
Type
Excl
Type
study
(n)
(n)
2001
S+N
2
xs
28-85
202
10
108
X
X
X
Leung
2006
S
1
xs
65%>60yrs
5,464
322
512
X
X
X
Mant
1989
B
2
c
40 – 95
144
16
11
X
X
Metcalf
1996
B
2
xs
40 -86
99
8
25
X
X
Morini
2001
S+N
1
xs
966
49
X
X
X
Nakama
2000
S+N
2
xs
9,625
31
X
Nakamura
1984
S+N
2
cc
251
100
X
Nascimbeni
2002
S+N
1
cc
39-95
151
55
X
Neugent
1993
S+N
2
xs
35-84
1,172
91
Norrelund
1996
B
2
c
364
54
Panzuto
2003
S+N
2
xs
18-87
280
41
Park
2006
S+N
1
xs
21-78
17,307
51
Pernu
1960
S+N
2
cc
2,439
666
X
Roberts
2003
S+N
1
cc
1,675
634
X
Robertson
2006
B
2
xs
18-97
604
22
Sardinha
1999
S+N
1
xs
80-95
428
10
Schoepfer
2005
S
2
xs
50-80
1,514
83
Selvachandran
2002
S
2
xs
2,268
95
Author
Year
Leis
age range
40-60+
275
4136
Bleeding
X
Abdo
pain
CBH
X
X
X
X
X
X
X
X
X
X
Constip
Diarrhoea
Weight
loss
Other
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
484
page 11 of 13
X
X
X
X
X
X
X
Pop
Mut
Design
No in
Cancer
Polyp
Type
Excl
Type
study
(n)
(n)
1994
S+N
2
xs
1,852
55
186
Tan
2002
S+N
2
xs
485
Tate
1988
S
2
xs
20-83
Thompson
2007
S
2
xs
52%> 60yrs
Vobecky
1983
S+N
2
Watanabe
2004
S+N
2
Wauters
2000
S
2
Wynder
1967
S+N
2
Wynder
1969
S+N
Zbar
1999
Zerey
2007
Author
Year
Steine
age range
Bleeding
Abdo
pain
CBH
Constip
Diarrhoea
Weight
loss
X
X
X
58
X
X
X
130
14
X
X
X
8,529
467
X
X
X
cc
414
207
X
c
41,670
251
X
7,886
106
cc
1,200
791
X
2
cc
464
157
X
S+N
1
xs
19-85
744
36
86
X
X
X
X
S+N
1
xs
85-99
157
8
108
X
X
X
X
40
33
31
combin
ed
X
Other
X
X
X
X
X
X
X
X
TOTAL
26
14
18
32
Notes:
Abdo pain = abdominal pain; constip = constipation X= reported
Pop type = population from which participants drawn: S=people with and with no symptoms N=all people had symptoms B=all had bleeding
Mut excl = mutually exclusive; refers to the number of symptoms that could be reported, ie whether or not the symptoms were mutually exclusive: 1=
only 1 symptom per participant 2= any number of symptoms could be reported for each participant
Design Type: xs = cross sectional analytical; cc= case control; c= cohort
page 12 of 13
Appendix 4 Bleeding type: association with cancer: DOR with 95% confidence intervals
Paper (Author)
Mixed
with
stool
On toilet
paper
Colours
water
On paper
and in
bowl
Separate
from
stool
Bjerregaard
Ellis
Fitjen
Jensen
Mant
Metcalf
Bright
red
0.9
(0.6-1.3)
1.0
(0.2-5.7)
3.4
(0.9-12.3)
3.2
(0.6-17.1)
2.6
(0.9-7.2)
1.9
(0.5-7.8)
0.6
(0.1-2.4)
0.4
(0.0-6.6)
0.8
(0.3-2.2)
1.2
(0.3-5.5)
1.4
(0.4-4.9)
0.9
(0.3-2.6)
Dark red
5.6
(3.6- 8.8)
2.8
(0.7-10.2)
Selvachandran
Large (vs
small)
volume
1.3
(0.4-4.1)
0.3
(0.1-1.8)
New (vs
changed
0.2
(0.1-0.6)
1.1
(0.2-5.1)
1.4
(0.3-5.8)
Norrelund
Robertson
First
episode
0.7
(0.3-1.5)
3.1
(1.2-8.1)
3.7
(2.3-5.8)
2.1
(1.2-4.0)
0.8
(0.5-1.2)
1.1
(0.7-1.6)
page 13 of 13
4.5
(1.9-10.6)
3.0
(1.4-6.6)